The main objective of our research is to learn more about the evolution of intracellular regulation. Using biochemical and genetic tools, we are studying the regulation of leucine biosynthesis in prokaryotes (Salmonella typhimurium and E. coli) and a lower eukaryote (Saccharomyces cerevisiae). While emphasis is on the first committed enzyme of the leucine pathway, alpha-isopropylmalate synthase, the other enzymes of the leucine pathway and their interaction are also being investigated. Mutants of S. cerevisiae affecting either feedback inhibition of the first leucine-specific enzyme or expression of the leucine genes have recently been isolated and are expected to yield important clues concerning the regulation of the leucine pathway in this organism.